Chiaramente, ogni formato ha i propri vantaggi e svantaggi comprare doxycycline senza ricetta per effettuare un acquisto, non è necessario fornire la prescrizione medica.
EFFICACY OF TADALAFIL FOR THE TREATMENT OF
ERECTILE DYSFUNCTION AT 24 AND 36 HOURS AFTER
DOSING: A RANDOMIZED CONTROLLED TRIAL
HARTMUT PORST, HARIN PADMA-NATHAN, FRANC
¸ OIS GIULIANO, GREG ANGLIN,
LUCIO VARANESE, AND RAYMOND ROSEN
To examine the therapeutic effects of tadalafil on erectile dysfunction (ED) at 24 and 36 hours
A multicenter, randomized, double-blind, placebo-controlled, parallel-group study of 348 men
(mean age 57 years) with ED was conducted in Europe and the United States. Patients were stratified by
baseline severity of ED using the Erectile Function domain score of the International Index of Erectile
Function and then randomly allocated within the severity group to receive tadalafil 20 mg (n ⫽ 175) or
placebo (n ⫽ 173). Subsequently, participants were randomly assigned to two 4-week treatment intervals,
during which they were requested to attempt sexual intercourse approximately 24 or 36 hours after tadalafil
or placebo dosing. The primary outcome measure was the proportion of successful sexual intercourse
attempts (completed to ejaculation) according to patient self-report using the Sexual Encounter Profile diary.Results.
Of the 348 patients, 327 (94%) completed the trial (163 of 175 in the tadalafil group and 164 of
173 in the placebo group). Thirty-six hours after tadalafil dosing, 59.2% of intercourse attempts were
successful versus 28.3% in the placebo group (P
⬍0.001). The proportion of successful intercourse attempts
at approximately 24 hours after treatment was also significantly greater with tadalafil (52.9%) than withplacebo (29.1%; P
⬍0.001). Tadalafil was well tolerated. The incidences of four treatment-emergent adverse
events were significantly greater in the tadalafil group than in the placebo group (all P
flushing, dyspepsia, and myalgia.Conclusions.
Tadalafil 20 mg is an effective and well-tolerated treatment for ED that has a period of
responsiveness of up to 36 hours. UROLOGY 62:
121–126, 2003. 2003 Elsevier Inc.
rectiledysfunction(ED)affectsmorethan150 Americans.1–3 Yet, reviews of published studies4
million men worldwide,1 including approxi-
have estimated that 70% of ED goes undiagnosed.
mately 20 million European men and 30 million
For the minority of these men who do seek help,
therapy with the oral, selective phosphodiesterase5 (PDE5) inhibitor sildenafil largely resolves ED,
This study was funded by Lilly ICOS LLC.
conferring benefits to both patients and their part-
H. Porst, H. Padma-Nathan, F. Giuliano, and R. Rosen are paid
ners.5–12 The efficacy of PDE5 inhibitors is ascribed
consultants to both the sponsor of this study and competitors, are
to their ability to amplify the activity of the nitric
study investigators funded by the sponsor, and are members of thespeaker's bureau for the sponsor. G. Anglin and L. Varanese are
oxide-3⬘,5⬘-cyclic guanosine monophosphate sig-
employees of the sponsor and hold stock in the sponsor.
naling pathway and to potentiate the smooth mus-
From Private Urological Practice, Hamburg, Germany; Uni-
cle-relaxing effects of nitric oxide within the cor-
versity of Southern California Keck School of Medicine, Los An-
pus cavernosum.13 However, despite its high
geles, California; Department of Urology, CHU de Biceˆtre, Le
efficacy rates, many men stop using sildenafil. The
Kremlin-Biceˆtre, France; Eli Lilly Canada, Toronto, Ontario,Canada; Eli Lilly, Erl Wood, United Kingdom; University of Med-
reasons for this include cost, adverse events, and
icine and Dentistry of New Jersey, Robert Wood Johnson Medical
perceived lack of efficacy.14 In addition, in a survey
School, Piscataway, New Jersey.
about the importance of different outcome vari-
Reprint requests: Hartmut Porst, M.D., Urological Practice,
ables when choosing among pharmacotherapies
Neuer Jungfernstieg 6a, Hamburg 20354, Germany
Submitted: September 5, 2002, accepted (with revisions):
for ED, the investigators found that success, avoid-
January 27, 2003
ing a negative outcome, and naturalness ranked
2003 ELSEVIER INC.
ALL RIGHTS RESERVED
highest.15 It is therefore possible that some men
ure to achieve erection after radical prostatectomy or pelvic
may discontinue sildenafil use because it makes
surgery, a history of stroke or spinal cord trauma in the pre-
sexual encounters feel less natural.
vious 6 months, unstable cardiac disease, clinically significantrenal insufficiency or hepatobiliary disease, and concomitant
On closer examination, the perceived lack of ef-
antiandrogen use or chemotherapy.
ficacy of sildenafil can usually be attributed to in-
To ensure balanced allocation, patients were stratified by
adequate dosing and failure by the physician to
baseline ED severity according to their scores on the Erectile
give thorough instructions (or of the patient to fol-
Function domain of the International Index of Erectile Func-
16 For instance, some patients who are
with mild ED characterized by a score of 17 to
25, moderate ED by a score of 11 to 16, and severe ED by a
regarded as sildenafil failures may not have re-
score of 1 to 10. Although scores of 26 to 30 are indicative of
ceived sufficient sexual stimulation before at-
no ED,21 those entering the study with scores of 26 or greater
tempting intercourse, and others may have at-
were added to the mild group for classification purposes. Pa-
tempted intercourse too early after dosing or after a
tients were randomized to tadalafil or placebo according to a
computer-generated randomization table. At the screeningvisit (4 weeks before randomization), patients underwent a
Tadalafil (Cialis, Lilly ICOS LLC, Indianapolis,
physical examination, 12-lead electrocardiogram, and labora-
Ind and Bothell, Wash) is a potent, reversible, and
tory tests. Vital signs (blood pressure and heart rate) were
selective PDE5 inhibitor for the treatment of ED.17
measured at each visit, and the physical examination was re-
Compared with sildenafil (Viagra, Pfizer, New
peated at week 8 or at premature discontinuation, if necessary,
York, NY), tadalafil has an extended terminal half-
at each investigator's discretion.
life, 17.5 hours18 versus 3.7 hours,19 suggesting alengthened period of responsiveness compared
The proportion of "yes" responses to Sexual Encounter Pro-
file (SEP) question 3 (SEP-Q3), "Did your erection last long
On the basis of the pharmacokinetic data, as well
enough for you to have successful intercourse? [yes/no]," rep-
as preliminary clinical evidence suggesting an ex-
resented the primary efficacy variable.
tended duration of action, this study was designed
Adverse events reported by patients were recorded at each
to evaluate the efficacy of tadalafil at 24 and 36
4-week visit, classified by severity, and coded using the
hours after dosing in men with ED.
COSTART (Coding Symbols for a Thesaurus of Adverse Reac-tion Terms) dictionary. Investigators also assessed the rela-tionship of each event to the study drug. The safety outcome
MATERIAL AND METHODS
measure was the incidence of treatment-emergent adverseevents in the placebo or tadalafil group. Treatment-emergent
STUDY DESIGN AND PATIENT POPULATION
adverse events were defined as events that first occurred or
This multicenter, randomized, double-blind, placebo-con-
worsened after the baseline assessment.
trolled, parallel-group trial was conducted at 36 centers inEurope and the United States from February through April2001. Ethical review boards approved its protocol and in-
formed consent documents, and all patients and partners pro-
Each randomized patient was eligible for the efficacy anal-
vided written informed consent before enrollment. The study
ysis. The analysis of safety included all randomized patients.
consisted of a 4-week treatment-free run-in period (during
All analyses were performed with the patients included in the
which patients qualified for randomization in part by attempt-
group to which they were assigned by random allocation. Pa-
ing sexual intercourse at least four times), followed by ran-
tient baseline characteristics were summarized for each treat-
domization in a 1:1 ratio to tadalafil 20 mg or matching pla-
cebo for 8 weeks.
For continuous patient characteristics at baseline, the mean
The treatment period was divided into two 4-week inter-
values by therapy group were compared using analysis of vari-
vals, each of which began with the investigator dispensing two
ance. The incidence of the categorical variables at baseline was
doses of treatment for at-home use. Each man was instructed
compared using the Pearson chi-square test.
to take one dose of treatment before sexual activity, with no
It was specified a priori that a sexual encounter that was
restrictions on alcohol or food intake. During one 4-week
recorded ⱖ20 hours or ⱕ30 hours after dosing was considered
phase, the patients were to attempt sexual intercourse twice in
an eligible 24-hour encounter if it was the first encounter after
conjunction with medication use, each time at approximately
dosing. Similarly, an encounter that was recorded ⱖ30 hours
24 hours after dosing, with an 8 to 10-day washout period
and ⱕ48 hours after dosing was considered an eligible 36-
hour encounter if it was the first encounter after dosing. How-
In the other 4-week interval, men were instructed to at-
ever, the data presented herein are for encounters made ⱖ22
tempt intercourse at approximately 36 hours after dosing, and
hours or ⱕ26 hours after dosing for the 24-hour time point
then repeat after another 8 to 10-day washout period. Patients
and for encounters made ⱖ34 hours or ⱕ38 hours after dosing
were also randomized into two order groups, with intercourse
for the 36-hour time point.
requested either 36 hours after dosing for the first 4-week
Two null hypotheses were tested in a sequential fashion.
interval, and then 24 hours after dosing for the second, or vice
The first was that there was no difference between tadalafil 20
mg and placebo in terms of the proportion of successful inter-
Men aged 18 years or older with a minimum 3-month his-
course attempts at 24 hours after dosing, as measured by SEP-
tory of ED who were in a stable, monogamous relationship
Q3. To reject this null hypothesis, significance at the 0.05 level
with a female partner were eligible for enrollment. ED was
was required. A second null hypothesis was tested only be-
defined as a consistent change in the quality of erection that
cause the first null hypothesis was rejected with P
adversely affected the patient's satisfaction with sexual inter-
there was no difference between tadalafil 20 mg and placebo in
course. Patient exclusion criteria included the presence of pe-
terms of the proportion of successful intercourse attempts at
nile implants or clinically significant penile deformities, fail-
36 hours after dosing, as measured by SEP-Q3. To reject this
UROLOGY 62 (1), 2003
signed to placebo (P
⬍0.001; Table II). On the
TABLE I. Baseline demographic
basis of positive responses to SEP-Q3, 120 (53%)
of 227 intercourse attempts at 24 hours were suc-
cessfully completed in the tadalafil group com-
pared with 72 (29%) of 247 in the placebo control
⬍0.001). Of the patients randomized to
placebo (n ⫽ 173), 144 had a sexual attempt at 24
hours and 128 at 36 hours. Approximately 37%
and 35% of these patients had a successful attempt
at 24 and 36 hours after dosing, respectively.
Among those randomized to tadalafil (n ⫽ 175),
138 and 131 patients had eligible encounters at 24
Severity of ED* (n)
and 36 hours after dosing, respectively. Of those,
61% had a successful intercourse attempt at 24
hours and 64% had a successful intercourse at-
tempt at 36 hours (P
Treatment with tadalafil was well tolerated. The
Current smoker (n)
incidences of treatment-emergent headache, flush-
Current alcohol use (n)
ing, dyspepsia, and myalgia were significantlygreater in the active-treatment arm compared
⫽ erectile dysfunction.
Numbers in parentheses are percentages.
with the placebo group (Table III). Notably, there
*Based on Erectile Function domain scores on the International Index of Erectile
were no visual-perceptual changes, cardiovascular
Function (mild, 17–30 [includes men with no ED, scores of 26 –30]; moderate,11–16; severe, 1–10).
events, or any clinically significant effects oftadalafil on electrocardiographic findings, heartrate, or blood pressure.
null hypothesis, significance at the 0.05 level was required.
The majority of adverse events were mild or
Each test was two-tailed.
moderate in severity. A total of 4 patients discon-
For primary efficacy analyses of SEP-Q3, the "yes"/"no"
tinued the study prematurely because of adverse
responses were considered in a categorical repeated-measures
events: 3 (2%) in the tadalafil group and 1 (0.5%)
model. The model included terms for treatment group, inves-tigative site, patient's baseline percentage "yes" responses to
in the placebo group. Of the 3 patients taking
SEP-Q3, and the baseline value of the Erectile Function do-
tadalafil who withdrew, 1 each experienced myal-
main of the International Index of Erectile Function. One
gia (with lethargy) after two doses; dyspepsia after
model was fitted for the responses for the 24-hour time point,
one dose; or abdominal pain (with nausea) after
and a separate model was fitted for the responses for the 36-
one dose. One placebo recipient experienced diz-
hour time point.
Safety was assessed by evaluating all reported adverse
ziness and headache.
events, vital signs, and physical examination results. Treat-ment-emergent adverse events were summarized by the
COSTART preferred term for severity and relationship tostudy drug. The analysis comparing the incidence of treat-
Because of their relatively short half-lives, phar-
ment-emergent adverse events among treatment groups was
macologic agents for ED have historically been
performed using Fisher's exact test.
used just before a couple engages in sexual activity,inextricably linking the medication with a man's
sexual performance. For example, with alprostadil
Of 348 men enrolled, 327 (94%) completed
injection (Caverject, Pharmacia & Upjohn, Pea-
treatment. The baseline characteristics were well
pack, NJ), erection is expected to occur within 5 to
balanced in the two treatment groups (Table I).
20 minutes after dosing and to last up to 1 hour,
The mean age in each group was 57 years, and most
regardless of sexual stimulation.22 With the alpros-
patients had ED for more than 1 year. On the basis
tadil urethral suppository (MUSE, Vivus, Moun-
of previously established Erectile Function domain
tain View, Calif), erection is expected to occur
categories of the International Index of Erectile
within 10 minutes of administration and to last for
Function, about 40% of men had mild ED, 35% had
30 to 60 minutes, with or without sexual stimula-
severe ED, and 25% had moderate ED.
tion.23 With sildenafil (Viagra, Pfizer, New York,
Tadalafil was effective for 36 hours, with 132
NY), men may experience erection between 30
(59%) of 223 intercourse attempts successfully
minutes and 4 hours after ingestion, and sexual
completed in patients randomized to the 20-mg
stimulation is required.24 For apomorphine
dose compared with 60 (28%) of 212 in those as-
(Ixense, Takeda Europe Research & Development
UROLOGY 62 (1), 2003
TABLE II. Effects of tadalafil on successful intercourse completion over time*
Numbers in parentheses are percentages.
*Proportion of successful intercourse attempts according to Sexual Encounter Profile Question 3 (SEP-Q3). For the requested 24-hr time point, first attempts made
ⱖ22 hr and
ⱕ26 hr after dosing were included; for the requested 36-hr time point, first attempts made
ⱖ34 hr and
ⱕ38 hr after dosing were included.
†P ⬍0.001 for comparison (tadalafil vs. placebo) from a repeated-measures logistic regression model of yes/no responses to SEP-Q3 for requested encounter.
tivity, causing them to plan their sexual encounters
TABLE III. Incidence of adverse events*
rather than allowing them to occur spontaneously.
Prior studies18 using successful intercourse com-
pletion (SEP-Q3) as the primary outcome measure
demonstrated that the earliest time to the onset of
significant effects for tadalafil 20 mg was 16 min-
utes after dosing (32% success rate versus 15%
with placebo; P
⬍0.05). At 30 minutes after dos-
Data presented as number of patients, with the percentage in parentheses.
ing, 52% of men were considered responders to
*Treatment-emergent adverse events of all causes either occurring in at least 3% ofeach treatment group or exhibiting a significant difference across treatment arms.
treatment versus 35% in the placebo group(P
The extended period of responsiveness afforded
Centre, London, United Kingdom), men may ex-
by tadalafil, which has a terminal half-life of 17.5
perience erection 20 minutes after sublingual ad-
hours, may begin to change the treatment para-
ministration, provided they have adequate sexual
digm for men with ED. Unlike currently available
stimulation, and can take a subsequent dose 8
treatments, tadalafil may, for example, enable a pa-
tient to take a pill on a Friday evening and have
In this trial, the ability of tadalafil to significantly
intercourse with his partner on Saturday night or
increase the percentage of successful intercourse
Sunday morning. The broad therapeutic coverage
attempts was still evident 36 hours after dosing,
conferred by tadalafil, which can be taken without
with approximately 60% of intercourse attempts
restrictions on alcohol or food intake, might trans-
successfully completed at this time point versus
late to enhanced convenience and simplicity of ad-
28% with placebo (P
⬍0.001). Tadalafil was well
ministration, traits that are valued by men with
tolerated and exhibited a tolerability profile consis-
tent with previously published data.17
This was not a study of efficacy per se or the time
of maximum efficacy; rather, it was designed todetermine whether tadalafil was associated with a
The advent of a pharmacologic agent such as
treatment effect that could be discriminated from
tadalafil, with a period of responsiveness that be-
the effect of placebo for at least 24 and 36 hours.
gins soon after dosing and lasts up to 36 hours, may
Standardized efficacy trials showed that approxi-
allow men and their partners more freedom in the
mately 75% of intercourse attempts were success-
timing of their sexual activity.
ful (as measured by SEP-Q3) among men treatedwith tadalafil 20 mg (P
⬍0.001 versus placebo),
with 80% success for attempts undertaken up to 24
1. McKinlay JB: The worldwide prevalence and epidemi-
hours after dosing.18 Differences among the rates
ology of erectile dysfunction. Int J Impot Res 12(
S6 –S11, 2000.
of successful sexual intercourse with tadalafil in
2. Phillips P: Reports at European Urology Congress re-
this study compared with standardized efficacy
flect issues of interest to aging men. JAMA 279:
trials are likely related to the study's design. In the
standardized efficacy trials, men were allowed to
3. NIH Consensus Conference. Impotence. NIH Consen-
take tadalafil at any time of their choosing before
sus Development Panel on Impotence. JAMA 270:
engaging in sexual activity. In this trial, patients
4. Chun J, and Carson CC: Physician-patient dialogue and
and their partners were required to wait a prespeci-
clinical evaluation of erectile dysfunction. Urol Clin North Am
fied amount of time before engaging in sexual ac-
249 –258, 2001.
UROLOGY 62 (1), 2003
5. Goldstein I, Lue TF, Padma-Nathan H, et al
, for the
25. Ixense威 (apomorphine hydrochloride) prescribing in-
Sildenafil Study Group: Oral sildenafil in the treatment of
formation. London, United Kingdom, Takeda Europe Re-
erectile dysfunction. N Engl J Med 338:
search & Development Centre, 2001.
6. Dinsmore WW, Hodges M, Hargreaves C, et al:
afil citrate (Viagra) in erectile dysfunction: near normalisationin men with broad-spectrum erectile dysfunction compared
EDITORIAL COMMENT 1
with age-matched healthy control subjects. Urology 53:
The world of ED changed forever at the 1983 American
Urological Association meeting in Las Vegas, when a British
7. McMahon CG, Samali R, and Johnson H: Efficacy,
physiologist named Giles Brindley stepped from behind the
safety and patient acceptance of sildenafil citrate as treatment
podium and lowered his pants, revealing to colleagues his
for erectile dysfunction. J Urol 164:
phentolamine-induced erection. Said one pundit of this water-
8. Rendell MS, Rajfer J, Wicker PA, et al
, for the Sildenafil
shed event, "Farther down the Strip, Siegfried and Roy were
Diabetes Study Group: Sildenafil for treatment of erectile dys-
making a white Bengal tiger disappear, and two circus aerial-
function in men with diabetes: a randomized controlled trial.
ists— one sitting on the other's shoulders—were traversing a
tightrope without a net. But even in Vegas they'd never seen a
9. Guay AT, Perez JB, Jacobson J, et al:
Efficacy and safety
show like this.
" Thus was crystallized the enduring principle
of sildenafil citrate for treatment of erectile dysfunction in a
that penile erection is caused by smooth muscle relaxation in
population with associated organic risk factors. J Androl 22:
the corpora cavernosa. Few breakthroughs in medical history
have been heralded with the dramatic impact of Brindley's
10. Hultling C, Giuliano F, Quirk F, et al:
Quality of life in
moment in Nevada.
patients with spinal cord injury receiving Viagra (sildenafil
Tadalafil (Cialis, Lilly ICOS LLC), along with sildenafil (Vi-
citrate) for the treatment of erectile dysfunction. Spinal Cord
agra, Pfizer) and vardenafil (Levitra, Bayer), belong to an
orally effective class of smooth muscle relaxants called phos-
11. Weber DC, Bieri S, Kurtz JM, et al:
phodiesterase (PDE) inhibitors. Unlike Brindley's direct-act-
study of sildenafil for treatment of postradiotherapy erectile
ing phentolamine, PDE5 (penile) inhibitors produce erections
dysfunction in patients with prostate cancer. J Clin Oncol 17:
indirectly, by inhibiting breakdown of cyclic guanosine mono-
3444 –3449, 1999.
phosphate, the neurotransmitter for corporal smooth muscle
12. Lewis R, Bennett CJ, Borkon WD, et al:
relaxation. Thus, with PDE5 inhibitors, erection develops in a
partner satisfaction with Viagra (sildenafil citrate) treatment
physiologic manner by amplification of the nitric oxide path-
as determined by the Erectile Dysfunction Inventory of Treat-
way and only with sexual stimulation. Sildenafil, the sole
ment Satisfaction Questionnaire. Urology 57:
960 –965, 2001.
PDE5 inhibitor currently approved in the United States, has
13. Ignarro LJ, Bush PA, Buga GM, et al:
Nitric oxide and
enjoyed enormous success because of its specificity, effective-
cyclic GMP formation upon electrical field stimulation cause
ness, convenience, and safety; according to Pfizer, more than
relaxation of corpus cavernosum smooth muscle. Biochem
20 million men in 110 countries have used the drug.
Biophys Res Commun 170:
In the present report of Phase III tadalafil data, 348 men
14. Madduri SD: After two years, did Viagra live up to its
with organic and/or psychogenic ED were given the drug (20
expectations? Missouri Med 98:
mg) or placebo in an 8-week randomized, multicenter trial.
15. Hanson-Divers C, Jackson SE, Lue TF, et al:
The trial was designed specifically to test the duration of ac-
outcomes variables important to patients in the treatment of
tion of the drug. Thirty-six hours after dosing, approximately
erectile dysfunction. J Urol 159:
two thirds of tadalafil patients, but only one third of placebo
16. El-Galley R, Rutland H, Talic R, et al:
patients, were able to have successful intercourse (P
cacy of sildenafil and tachyphylaxis effect. J Urol 166:
Side effects were uncommon and not severe, including mostly
the now-familiar headache, flushing, and dyspepsia. A fewpatients also reported myalgias, possibly because of skeletal
17. Brock G, McMahon CG, Chen KK, et al:
muscle PDE inhibition. Only 3 of 175 tadalafil patients discon-
safety of tadalafil in the treatment of erectile dysfunction: re-
tinued the trial prematurely because of adverse events. Thus,
sults of integrated analyses. J Urol 168:
the data support the authors' statement that tadalafil is effec-
18. Rosen RC, Padma-Nathan H, Shabsigh R: Cialis
tive and well tolerated.
(IC351) provides prompt response and extended period of
What distinguishes tadalafil pharmacologically is its long
responsiveness for the treatment of men with erectile dysfunc-
duration of action, relative selectivity for PDE5, and bioavail-
tion (ED). Program and abstracts of the 96th Annual Meeting
ability independent of food intake. The drug has a half-life of
of the American Urological Association, June 2–7, 2001, Ana-
17.5 hours compared with 4 hours for sildenafil, earning
tadalafil the nickname "weekender." Clearly, tadalafil could be
19. Walker DK, Ackland MJ, James GC, et al:
taken on Friday and continue to enhance erectile function for
netics and metabolism of sildenafil in mouse, rat, rabbit, dog,
at least the next several days without redosing. This conve-
and man. Xenobiotica 29:
nience must be weighed against the possibility of a lingering
20. Rosen RC, Riley A, Wagner G, et al:
undesirable effect in some men. In Europe, where the drug
Index of Erectile Function (IIEF): a multidimensional scale
was approved in November 2002, the package leaflet carries a
for assessment of erectile dysfunction. Urology 49:
stern warning ("Do not take Cialis") not only for men using
organic nitrates and nitric oxide donors, but also men with
21. Cappelleri JC, Rosen RC, Smith MD, et al:
serious heart disease, recent stroke or myocardial infarction,
evaluation of the Erectile Function domain of the Interna-
and uncontrolled blood pressure (high or low). The Viagra
tional Index of Erectile Function. Urology 54:
346 –351, 1999.
warning is similar.
22. Caverject威 (alprostadil injection) prescribing informa-
Just how tadalafil will fit into our therapeutic armamentar-
tion. Kalamazoo, Michigan, Pharmacia & Upjohn, 1999.
ium vis-a -vis other PDE5 inhibitors (and future remedies un-
23. MUSE威 (alprostadil urethral suppository) patient in-
known) will not become clear until the widespread use ex-
formation. Mountain View, California, Vivus, 1998.
pected after Food and Drug Administration approval. What is
24. Viagra威 (sildenafil citrate) prescribing information.
clear, however, is that the pre-Brindley world of ED—a world
New York, New York, Pfizer, 2000.
largely consisting of testosterone injections, psychotherapy,
UROLOGY 62 (1), 2003
Los Teques MeTro venezuela invests in rePAr: buiLding 8 refinery uniTs AT once brAskeM rAises funds wiTh MegA deAL ciTy of sALvAdor geTs second MArine ouTfALL [ TEO ] Odebrecht Entrepreneurial Technology"Everything we have built will only maintain its value if,
O'Shaughnessy's • Winter 2015/16 —7— Cannabis in the Treatment of Pediatric Epilepsy By Bonni Goldstein, MD The author documents the progress of more than 100 patients using CBD-rich cannabis oil to treat seizure disorders. I have been a medical cannabis physician seeing adult tion they are going to give their child. They cannot give oil, the added expense of testing every bottle becomes pro-